Dataset Information

Prenatal stress and offspring depression in adulthood: The mediating role of childhood trauma.

ABSTRACT:

Background

There is repeated evidence for a prenatal programming effect for the development of offspring depression. However, examination of environmental influences along this pathway is sparse. This study aimed to investigate the direct and indirect effects of pre- and postnatal stress on offspring depression in adulthood, via increased exposure to childhood trauma.

Methods

A large longitudinal population-based cohort (N = 3506) was followed up from birth and assessed at 24 years. Diagnosis of depression was derived using the International Classification of Diseases-10th revision (ICD-10). Two separate sources of pre- and postnatal stress were examined - maternal depression and family adversity, and childhood trauma was assessed prospectively across childhood until 17 years.

Results

Both pre- and postnatal maternal depression and family adversity were associated with offspring depression at 24 years in simple logistic regression models. When all pathways were modelled simultaneously, only childhood trauma was directly associated with offspring depression, and mediated all pathways from both sources of pre- and postnatal stress to offspring depression (7-16% of the total effect mediated). Sensitivity analysis on specific trauma found stronger evidence for a mediated pathway via physical, emotional abuse and peer bullying, compared to emotional neglect, sexual abuse and domestic violence.

Conclusions

These findings indicate that reducing childhood trauma could be a target to decrease depression in the general population, and the focus should also be on families at high risk of experiencing pre- or postnatal stress, to provide them with better support.

SUBMITTER: Liu Y

PROVIDER: S-EPMC8641663 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.

Project description:ObjectivesThe present study sought to assess the relationship between depressive symptomatology and resilience among women infected with HIV and to investigate whether trauma exposure (childhood trauma, other discrete lifetime traumatic events) or the presence of post-traumatic stress symptomatology mediated this relationship.DesignCross-sectional study.SettingWestern Cape, South Africa.ParticipantsA convenience sample of 95 women infected with HIV in peri-urban communities in the Western Cape, South Africa. All women had exposure to moderate-to-severe childhood trauma as determined by the Childhood Trauma Questionnaire.Primary and secondary outcome measuresWe examined the relationship between depressive symptomatology and resilience (the Connor-Davidson Resilience Scale) and investigated whether trauma exposure or the presence of post-traumatic stress symptomatology mediated this relationship through the Sobel test for mediation and PLS path analysis.ResultsThere was a significant negative correlation between depressive symptomatology and resilience (p=<0.01). PLS path analysis revealed a significant direct effect between depression and resilience. On the Sobel test for mediation, distal (childhood trauma) and proximal traumatic events did not significantly mediate this association (p=>?0.05). However, post-traumatic stress symptomatology significantly mediated the relationship between depression and resilience in trauma-exposed women living with HIV.ConclusionsIn the present study, higher levels of resilience were associated with lower levels of self-reported depression. Although causal inferences are not possible, this suggests that in this sample, resilience may act as protective factor against the development of clinical depression. The results also indicate that post-traumatic stress symptoms (PTSS), which are highly prevalent in HIV-infected and trauma exposed individuals and often comorbid with depression, may further explain and account for this relationship. Further investigation is required to determine whether early identification and treatment of PTSS in this population may ameliorate the onset and persistence of major depression.

Project description:The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of maternal prenatal and infant nutritional status (from conception until early childhood) as well as maternal prenatal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early interventions.